This disclosure relates to a method for introducing substances into cells comprising contacting a composition comprising orally administered beta-glucan with said cells. A feature of this invention provides a method for introducing substances into a subject comprising administering to the subject an effective amount of the above compositions. The substance which could be delivered orally includes but is not limited to peptides, proteins, RNAs, DNAs, chemotherapeutic agents, biologically active agents, and plasmids. Other small molecules and compounds may be used as well. Another feature of the present invention is a composition comprising orally administered beta-glucan capable of enhancing efficacy of IgM antibodies.
Glucans derived from cell walls of yeasts, such as Saccharomyces cervisiae or mutant yeast strains described in U.S. Pat. No. 5,250,436, the disclosure of which is incorporated herein in its entirety by reference, may be used in the above compositions. Glucans having β(1-3) and β(1-6) linkages may be prepared by the process described in U.S. Pat. Nos. 5,233,491 and 4,810,646, the disclosures of which are incorporated herein in their entirety by reference. Soluble or aqueous glucans which are suitable for oral administration may be produced by the process described in U.S. Pat. Nos. 4,810,646 and 5,519,009, the disclosures of which are incorporated herein in their entirety by reference.
Beta-glucans have been tested for tumor therapy in mice for nearly 40 years.1,2 Several forms of mushroom derived beta-glucans are used clinically to treat cancer in Japan, including PSK (from Coriolus versicolor), Lentinan and Schizophyllan. In randomized trials in Japan, PSK has moderately, but significantly improved survival rates in some cancer trials: after gastrectomy,3,4 colorectal surgery,5,6 and esophagectomy7 to remove primary tumors. Results have been less encouraging in breast cancer,8,9 and leukemia.10 Schizophyllan has improved survival of patients with operable gastric cancer,11 inoperable gastric cancer,12,13 and cervical cancer.14 Again, though survival differences between groups were statistically significant, these improvements were modest. While beta-glucans are not widely used by Western oncologists, beta-glucan containing botanical medicines such as Reishi and maitake15 are widely used by U.S. cancer patients as alternative/complementary cancer therapies. These previous studies that looked for a therapeutic effect of beta-glucan, did not incorporate co-administration of therapeutic monoclonal antibodies (MoAb) as part of the protocol. There is increasing evidence that antibody is necessary to deposit iC3b which acts as a potent opsonin of human tumors. When beta-glucan is administered without co-administration of MoAb, its tumor cytotoxic effect requires the presence of naturally-occurring antitumor antibodies which can be quite variable among patients and even in experimental mice.
Anti-tumor effect of beta-glucan when combined with cancer specific antibodies was previously described. Previous studies have shown that oral beta-glucans derived from barley or oats can greatly enhance the anti-tumor activity of anti-tumor monoclonal antibodies in xenograph models. See Therapy-Enhancing Glucan, Int'l Application No. PCT/US02/01276, filed Jan. 15, 2002. Cheung et al., Oral (1-3),(1-4)-beta-glucan syngergizes with anti-ganglioside GD2 monoclonal antibody 3F8 in the therapy of neuroblastoma. Clin Cancer Res. 2002; 8:1217-1223. Cheung N K et al., Orally administered beta-glucans enhance anti-tumor effects of monoclonal antibodies. Cancer Immunol Immunother. 2002; 51:557-564. The phase I clinical trial supports the prediction that barley beta-glucan can enhance the antibody effect on metastatic cancer. As previously noted, lentinan and laminarin, both (1→3),(1→6)-β-D-glucans, were not as effective as barley glucan.16 In addition, among the (1→3),(1→4)-β-D-glucans, small molecular weight preparations and Lichenans were not as effective. The molecular size and the fine structure of beta-glucan may have substantial influence on their synergistic effect on antibodies towards tumors.
In Europe and USA beta-glucans especially from Bakers' yeast have long been employed as feed additives for animals, as dietary supplement for humans,17 in treatment of wounds,18 and as an active ingredient in skin cream formulations. The basic structural unit in beta-glucans is the β(1→3)-linked glucosyl units. Depending upon the source and method of isolation, beta-glucans have various degrees of branching and of linkages in the side chains. The frequency and hinge-structure of side chains determines its immunomodulor effect. beta-glucans of fungal and yeast origin are normally insoluble in water, but can be made soluble either by acid hydrolysis or by derivatisation introducing charged groups like -phosphate, -sulphate, -amine, -carboxymethyl and so forth to the molecule.19,20 
Soluble glucan with the molecular structure where (1→3)-β-D-glucan units form the backbone with branches made up of (1→3)-β-D-glucan units positioned at (1→6)-β-D-glucan hinges was isolated from Baker's yeast, Saccharomyces cerevisiae. High molecular weight fractions were obtained and
tested for synergy with monoclonal antibodies in tumor models. The anti-tumor effect of soluble yeast beta-glucan was found to be comparable to the anti-tumor effect of soluble barley beta-glucan, when combined with monoclonal antibodies specific for human cancer as detailed below.